SVR4 and SVR12 with an interferon-free regimen of BI AND BI , +/- ribavirin, in treatment-naïve patients with chronic genotype-1 HCV infection: Interim results of SOUND-C2 Stefan Zeuzem, 1 Vicente Soriano, 2 Tarik Asselah, 3 Jean-Pierre Bronowicki, 4 Ansgar W. Lohse, 5 Beat Müllhaupt, 6 Marcus Schuchmann, 7 Marc Bourliere, 8 Maria Buti, 9 Stuart Roberts, 10 Ed Gane, 11 Jerry O. Stern, 12 George Kukolj, 12 Luyan Dai, 12 Wulf O. Böcher, 13 Federico J. Mensa 13 1 Klinikum der J. W. Goethe-Universität, Frankfurt am Main, Germany; 2 Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain; 3 Hôpital Beaujon, Clichy, France; 4 Hôpital de Brabois, Vandoeuvre, France; 5 University Hospital Hamburg- Eppendorf, Hamburg; 6 University Hospital of Zurich, Zurich, Switzerland; 7 University Hospital Mainz, Mainz, Germany; 8 Hopital Saint Joseph, Marseille Cedex, France; 9 Hospital Vall d’Hebron, Barcelona, Spain; 10 Alfred Hospital, Department of Gastroenterology, Melbourne, Australia; 11 Auckland Clinical Studies, Auckland, New Zealand; 12 Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT, USA; 13 Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany

Speaker declaration I have financial relationships within the last 12 months relevant to my presentation with Boehringer Ingelheim Pharmaceuticals My presentation includes discussion of off-label or investigational use of: BI BI Ribavirin Other affiliations or financial interests: Abbott, Achillion, AstraZeneca, BMS, Gilead, Inhibitex, iTherX, Janssen, Merck, Novartis, Pharmasset, Roche, Santaris, Tibotec, Vertex

Background Phase Ib study of BI BI RBV (SOUND-C1) 1 : –100% RVR achieved in BI mg TID group –No severe AEs or discontinuations due to AEs during 4 weeks’ treatment BI BI nd generation protease inhibitor Nanomolar potency in vitro PK profile supportive of QD dosing Non-nucleoside NS5B inhibitor Nanomolar potency in vitro PK profile supportive of BID or TID dosing 1. Zeuzem S, et al. Gastroenterology 2011;141:2047–2055

Study design Phase IIb, multicentre, open-label, randomised (1:1:1:1:1) a Treatment-naïve patients with chronic HCV GT-1 Stratified by GT-1 subtype (1a vs 1b) and IL28B genotype (CC vs non-CC) Compensated cirrhosis allowed; 18–75 years of age, HCV RNA > IU/mL Primary endpoint: SVR 12 All analyses are ITT a Randomisation to the TID28W, no RBV arm was stopped early due to FDA feedback on protocol design after 46 patients were randomised Initial doses of 240 mg (BI ) and 1200 mg (BI ) were given on the first day of treatment; RBV dosed at 1000 mg/day (<75 kg body weight) or 1200 mg/day (≥75 kg body weight) BID, twice daily; QD, once daily; TID, three-times daily Follow-up BI mg QD + BI mg TID + RBV BI mg QD + BI mg TID + RBV BI mg QD + BI mg BID + RBV BI mg QD + BI mg TID, no RBV (n=81) (n=80) (n=77) (n=78) (n=46) Day 1 Week 16 Week 28 Week 40 Follow-up

Baseline characteristics TID16W (n=81) TID28W (n=80) TID40W (n=77) BID28W (n=78) TID28W, no RBV (n=46) Male, n (%)45 (56)41 (51)36 (47)41 (53)24 (52) White, n (%)79 (98)78 (98)76 (99)77 (99)46 (100) Mean age, years (SD)48.6 (11.3)47.3 (11.2)48.9 (10.7)47.9 (11.1)45.3 (13.0) Mean BMI, kg/m 2 (SD)25.3 (4.1)25.5 (4.1)24.8 (3.8)25.0 (3.6)25.5 (3.8) Liver cirrhosis, n (%)9 (11)7 (9)5 (7)13 (17)3 (7) IL28B a GT C/C, n (%)21 (26) 19 (25)19 (24)12 (26) HCV GT-1a b, n (%)34 (42)32 (40)34 (44)30 (38)18 (39) HCV GT-1b b, n (%)47 (58)48 (60)43 (56)48 (62)28 (61) Baseline HCV RNA c, n (%) ≥800,000 IU/mL 70 (86)66 (83)67 (87)66 (85)36 (78) a IL28B SNP rs b HCV GT-1 subtype analyses with TRUGENE ®, if GT result unspecified INNO-LiPA 2.0 c Plasma HCV RNA was measured using the Roche COBAS ® TaqMan HCV/HPS assay v2.0, with a lower limit of quantification (LLOQ) of 25 IU/mL and a lower limit of detection (LLOD) of approximately 15 IU/mL

Primary endpoint: Sustained virological response (ITT) a SVR a (%) 43/7748/8149/8053/7818/46 TID 16 + TID 28 + TID 40 + BID 28 + TID 28 - a Data for 40-week group are SVR4 rates as SVR12 data are not yet available SVR: HCV RNA undetected at 4 weeks (SVR4) and 12 weeks (SVR12) after treatment completion All groups received BI mg QD for the same duration as BI (16, 28 or 40 weeks) 7127 dosing Duration (weeks) RBV +/-

SVR according to subtype (GT-1a and GT-1b) (ITT) GT-1a GT-1b a Data for 40-week group are SVR4 rates as 12-week data not yet available All groups received BI mg QD for the same duration as BI (16, 28 or 40 weeks) TID 16 + TID 28 + TID 40 + BID 28 + TID dosing Duration (weeks) RBV +/-

SVR according to IL28B GT (CC vs non-CC) (ITT) Non-CC CC a Data for 40-week group are SVR4 rates as 12-week data not yet available All groups received BI mg QD for the same duration as BI (16, 28 or 40 weeks) TID 16 + TID 28 + TID 40 + BID 28 + TID dosing Duration (weeks) RBV +/-

SVR according to IL28B GT and viral subtype BID28W: 1a non-CC vs 1b (all) + 1a-CC (ITT) a non-CC1a CC1b non-CC1b CC SVR (%) 7127 dosing Duration (weeks) RBV +/- BID 28 +

SVR according to IL28B GT and viral subtype 1a non-CC vs 1b (all) + 1a-CC (ITT) SVR a (%) 1a non-CC All 1b and 1a-CC a Data for 40-week group are SVR4 rates as 12-week data not yet available All groups received BI mg QD for the same duration as BI (16, 28 or 40 weeks) TID 16 + TID 28 + TID 40 + BID 28 + TID dosing Duration (weeks) RBV +/-

On-treatment failures and relapse 1b (all) and 1a-CC a On-treatment failure = breakthrough On-treatment failure a Relapse TID 16 + TID 28 + TID 40 + BID 28 + TID dosing Duration (weeks) RBV +/-

On-treatment failures and relapse 1a non-CC On-treatment failure a Relapse TID 16 + TID 28 + TID 40 + BID 28 + TID dosing Duration (weeks) RBV +/- a On-treatment failure = breakthrough

Common AEs: Severity and discontinuations Number (%) of patients TID16W (n=81) TID28W (n=80) TID40W (n=77) BID28W (n=78) TID28W, no RBV (n=46) D/C due to AEs4 (4.9)10 (12.5)19 (24.7)6 (7.7)5 (10.9) Photosensitivity AEs Moderate4 (5)3 (4)6 (8)00 Severe01 (1)2 (3)00 Jaundice AEs Moderate2 (3)6 (8)3 (4)2 (3)0 Severe00000 Rash AEs Moderate2 (3) 04 (9) Severe1 (1)0 00 Vomiting AEs Moderate4 (5)10 (13)3 (4) 2 (4) Severe004 (5)01 (2) Diarrhoea AEs Moderate1 (1)4 (5)3 (4)4 (5)2 (4) Severe001 (1)00 Rash graded as moderate (diffuse, 30% to 70% body surface area) or severe (generalised, or mucous membrane involvement, organ dysfunction, anaphylaxis or life threatening) by rash management plan Other AEs judged per patient tolerability as moderate (interference with usual activity) or severe (incapacitating or causing inability to work or to perform usual activities)

Worst grade 3 and 4 lab abnormalities on treatment TID16W (n=81) TID28W (n=80) TID40W (n=77) BID28W (n=78) TID28W, no RBV (n=46) Haemoglobin Grade 302 (3)3 (4)1 (1)0 Grade (1)0 White cells Grade Grade Platelets Grade Grade ALT/GPT Grade 31 (1)002 (3)0 Grade Total bilirubin a Grade 333 (41)15 (19)20 (26) 6 (13) Grade 44 (5)10 (13)5 (6)10 (13)0 a All patients had a predominance of unconjugated bilirubin (UGT 1A1 inhibition) Gradings based on (Division of AIDS (DAIDS) gradings for laboratory abnormalities

Conclusions The IFN-free combination of BI BI RBV demonstrated high efficacy and a good safety profile 16 to 28 weeks of treatment with BI BI RBV achieved high SVR rates Up to 82% of GT-1a (IL28B: CC) and GT-1b patients (IL28B: CC + non-CC) achieved SVR Rates of on-treatment failure and relapse were low in this patient population Combination with ribavirin remains necessary The BID (for BI ) regimen demonstrated the a favourable safety and tolerability profile with a low rate of discontinuation Mostly mild effects on RBC and no effect on WBC and PLT counts were observed Sub-analysis of cirrhotic population in SOUND-C2: Poster 1420 in the late breaker area of the poster hall today Phase III studies investigating the BID regimen in the 1a-CC and 1b population are planned

Acknowledgements Patients and study investigators at study centres in the following countries: Boehringer Ingelheim for sponsoring the study and their clinical and statistical teams for study monitoring, data collection and analysis Editorial support provided by Nicky French of Adelphi Communications Ltd and funded by Boehringer Ingelheim AustraliaGermanyRomania Peter AngusKeikawus ArastéhEmanoil Ceausu Stuart RobertsThomas BergLiliana Preotescu AustriaMichael GeisslerAdrian Streinu-Cercel Peter FerenciAnsgar LohseSpain Michael GschwantlerMichael MannsMaria Buti Andreas MaieronStefan MaussJosé Luis Calleja FranceMarcus SchuchmannMoises Diago Tarik AsselahStefan ZeuzemXavier Forns Marc BourliereNew ZealandJavier Garcia-Samaniego Jean-Pierre BronowickiEd GaneVicente Soriano Dominique LarreyPortugalSwitzerland Joseph MoussalliFilipe CalinasTilman Gerlach Stanislas PolGuilherme MacedoMarkus Heim Jean-Pierre ZarskiLeopoldo MatosDarius Moradpour Fabien ZoulimCélia OliveiraBeat Müllhaupt Cristina ValenteJürg Reichen